Establishment of the specific cell-cell interactions required in nervous systems almost certainly requires the participation of unique cell surface and extracellular matrix components. The ability of neuronal cells to distinguish themselves from others, migrate to specific sites, and elaborate ordered functional connections is likely to depend upon interactions among complex arrays of cell membrane-associated molecules. The expression of specific surface constituents may thus establish the identity of individual neuronal cell types and function in the development and maintenance of specific intercellular interactions. Our primary recent interest has been in glycoconjugate molecules specifically associated with cone, as opposed to rod, photoreceptor cells in the neural retina. This interest was spurred by the observation that the lectin peanut agglutinin (PNA) binds specifically to cones in a variety of vertebrate retinae. We have begun the characterization of retinal molecules bound by PNA and have prepared cone-specific immunologic probes. In the proposed studies we wish to characterize further the biochemistry of molecules expressed by cone photoreceptors and examine possible roles for such molecules in the development, differentiation, and function of the retina. Retinal molecules bound by cone-specific antibodies will be characterized biochemically, their ultrastructural localization determined immunocytochemically, and their cross reactivity with retinae in a variety of species as well as with other neural and non-neural tissues will be assessed. The expression of cone-specific molecules during retinal development and in association with hereditary retinal degeneration will also be monitored. The biochemical characteristics of cone-specific domains in the interphotoreceptor matrix and their cellular source of will be investigated. Finally, the differentiation-dependent expression of glycoconjugate molecules by retinoblastoma cells in vitro will be monitored with the intent to relate such molecular changes to differentiative events in the developing retina and tumorigenicity of retinoblastoma cells.